The control of chondroitin sulphate biosynthesis and its influence on the structure of cartilage proteoglycans.
Chondroitin sulphate synthesis on proteoglycans was decreased in rat chondrosarcoma cell cultures in the presence of cycloheximide (0.1-1.0 muM) or p-nitrophenyl beta-D-xyloside (50 microM). In the presence of cycloheximide the proteoglycan monomer was of larger size, the chondroitin sulphate chains were increased in length, but a similar number of chains was attached to each proteoglycan and the size of the core protein was unaltered. In the presence of p-nitrophenyl beta-D-xyloside (50 microM), chondroitin sulphate synthesis was increased (by 60-80%), but the incorporation into proteoglycans was decreased (by 70%). The chondroitin sulphate chains were of shorter length than in control cultured and the number of chains attached to each proteoglycan was decreased. In cultures with cycloheximide or actinomycin D the synthesis of chondroitin sulphate was less inhibited on beta-xyloside than on endogenous proteoglycan. When the rate of chondroitin sulphate synthesis was decreased by lowering the temperature of cultures, the chains synthesized at 22 and 4 degrees C were much longer than at 37 degrees C, but in the presence of p-nitrophenyl beta-D-xyloside the chains were of the same length at all three temperatures. A model of chain elongation is thus proposed in which the rate of chain synthesis is determined by the concentration of xylosyl acceptor and the length of the chains is determined by the ratio of elongation activity to xylosyl-acceptor concentration.
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D002807:Chondroitin / Q000031:analogs & derivatives*; D002809:Chondroitin Sulfates / Q000096:biosynthesis*; D002813:Chondrosarcoma / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006027:Glycosides / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D013696:Temperature
D006027:Glycosides; D011509:Proteoglycans; D003609:Dactinomycin; C008646:4-nitrophenyl beta-D-xyloside; D002807:Chondroitin; D002809:Chondroitin Sulfates; D003513:Cycloheximide